Endocrine system anatomy and physiology

The endocrine system is made up of various endocrine glands that each secrete hormones into the bloodstream.

When hormones reach their target cell, they bind to a receptor on the cell’s membrane or within that cell, and in response the target cell changes what it’s doing.

So at the end of the day, the endocrine system helps establish homeostasis - a sense of balance even when there are changes in the external environment.

Now, structurally, hormones can be either steroids or non-steroids.

Steroid hormones are made from cholesterol, and they’re made by the adrenal glands, which sit above each kidney, and the gonads - either the testes or ovaries.

Steroid hormones are hydrophobic or non-polar - meaning that they hate watery environments, so they travel through the bloodstream bound to transport proteins to reach their target cells.

But because steroid hormones are relatively small, and non-polar, they are also able to diffuse right across phospholipid membrane of target cells. Once inside the cell, they bind to a receptor that goes on to activate certain genes in the nucleus.

Non-steroid hormones, on the other hand, are either peptides or proteins - so chains of amino-acids, or they can derive from a single amino acid.

Peptidic hormones, like insulin and glucagon, are hydrophilic - meaning they love coursing through our blood.

However, when they reach the cell membrane of a target cell, they can’t pass through the phospholipid bilayer. Instead, they bind to cell surface receptor proteins.

Once the receptors bind to a non-steroid hormone, they change shape, and that activates various proteins and enzymes that go on to create changes in gene expression within the cell.

So ultimately, once the non-steroid hormone binds to the receptor, there’s a change in the cell even though the hormone never actually enters the cell.

Finally, there are amino-acid hormones that derive from the amino acid, tyrosine, which are the thyroid hormones, as well as adrenaline and noradrenaline - also called epinephrine and norepinephrine. Now, these hormones are synthesized differently, so the molecular tweaks here and there make them behave differently; either more like steroids, or like peptides.

Thyroid hormones for example, behave more like steroid hormones: they travel the bloodstream bound to a transport protein, and cross the cell membrane to bind to an intracellular receptor, and signal changes in gene expression in the nucleus.

Adrenaline and noradrenaline, on the other hand, behave more like peptide hormones - they travel through blood unbound, and bind to cell surface receptors on cells, which then set off intracellular changes. In fact, that’s partly responsible for the increased blood flow to the heart and muscles, that occurs during a fight-or-flight response, when you’re fighting with an airline so you can catch a flight.

Now, the endocrine glands are scattered throughout the body, much like a remote work environment - so let’s get acquainted with our crew here.

All the way up into the brain, there’s the hypothalamus - which is like the CEO, and right below it, the first officer, the pituitary gland.

The hypothalamus and pituitary are physically connected by a thin stalk, and they work closely together to make hormones that help control the production of other endocrine glands, like the thyroid, the adrenal glands, and the gonads.

The hypothalamus is made up of several nuclei which are clusters of neurons with various roles, including secretion of hormones.

The pituitary gland is made up of two lobes - the anterior lobe, which is made up of glandular tissue, and the posterior lobe, which is made up of the axons of neurons coming down from the supraoptic and paraventricular nucleus in the hypothalamus.

Now, the hypothalamus is the link between the nervous and the endocrine system - it receives information from the entire body regarding all sorts of things - such as body temperature, blood osmolarity, or even if there’s some sort of danger - and it responds by producing hormones that are stored in the posterior pituitary, to be released later, or hormones that act on the anterior pituitary, making it secrete some hormones of its own. So the hypothalamus gives the order, and the pituitary enforces it.

This is possible because there are anatomical connections between the hypothalamus and both the anterior and posterior pituitary.

Between the hypothalamus and the anterior lobe of the pituitary, there’s the hypothalamo-hypophyseal-portal system. This is a system of tiny capillaries that moves hormones quickly from the hypothalamus to the anterior pituitary.

These hypothalamic hormones can be stimulatory or inhibitory. Let’s start with the stimulatory, or releasing, hormones. These include thyrotropin releasing hormone, or TRH; corticotropin releasing hormone, or CRH; gonadotropin releasing hormone, or GnRH and growth hormone releasing hormone, or GHRH.

These stimulatory hormones make the anterior pituitary synthesize its own hormones in response.

TRH leads to the production of thyroid stimulating hormone, or TSH, which reaches the thyroid and tells it to make some more thyroid hormones.

When plasma thyroid hormone levels increase, this sends a negative feedback signal to the pituitary to make less TSH, keeping thyroid hormone levels in an optimal range.

Next, there’s CRH, which makes the pituitary produce adrenocorticotropic hormone - or ACTH - which goes to the adrenal glands and makes them secrete more of a hormone called cortisol.

As before, high levels of cortisol inhibit the production of ACTH through a negative feedback mechanism.

Next, there’s GnRH which makes the pituitary secrete gonadotropins - follicle-stimulating hormone, or FSH, and luteinizing hormone, or LH.

Gonadotropins act on the gonads and regulate the production and maturation of gametes - sperm for the testes and oocytes for the ovaries, as well as the production of sex hormones - testosterone, estrogen and progesterone.

As a general rule, sex hormones also send a negative feedback mechanism back to the pituitary. The exception is that in females, right before ovulation, estrogen levels get really high, and they make the pituitary even more sensitive to hypothalamic GnRH. So this acts as a positive feedback signal, leading to a massive surge of FSH and LH that leads to ovulation.

Finally, GHRH makes the anterior pituitary secrete more growth hormone - or GH - which has a direct effect on the long bones and other tissues in our body, making them, well… grow.

So those were the stimulatory hypothalamic hormones. The inhibitory hypothalamic hormones are much easier to remember; there are only 2: growth hormone inhibiting hormone, or GHIH, also known as somatostatin, and prolactin inhibiting factor, which is also called dopamine.

GHIH is also synthesized by other organs in our body, like our digestive tract, and it tells the pituitary to secrete less growth hormone.

Now, with prolactin inhibiting factor, things are a bit trickier. Because prolactin increases milk production in the breasts, it’s only needed during breastfeeding.